tbuckley/cabot-search huggingface dataset:
Toripalimab combined with gemcitabine and S-1 in the first-line treatment of advanced biliary tract cancer.
Authors: Wei Li, Yueqi Wang, Yiyi Yu, Qian Li, Yan Wang, Chenlu Zhang, Xiaojing Xu, Xi Guo, Yuehong Cui, Qing Hao, Lujia Huang, Houbao Liu, Tianshu Liu
Journal: Journal of Clinical Oncology (2022)

4081 Background: Gemcitabine combined with platinum/fluorouracil drugs is the standard first-line treatment for advanced biliary tract cancers (BTCs), but the overall effect needs to be further improved. This study intended to explore the safety and efficacy of toripalimab combined with chemotherapy in the first-line treatment of advanced BTCs. Methods: This single-arm, phase II clinical trial enrolled patients with advanced BTCs who had not received systemic treatment. Toripalimab combined with chemotherapy were applied as first-line treatment: toripalimab (240 mg, iv, d1), gemcitabine (1000 mg/m2, iv, d1&amp;d8), and S-1 (40-60mg bid po, d1-14, Q21d). The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR) and safety. The study explored the association between response with PD-L1 expression, tumor mutational burden (TMB) and genetic variations identified by next-generation sequencing (NGS) of peripheral blood. Results: 50 patients were enrolled from January 2019 to August 2021 with a median follow-up time of 24.0 months (4.3-31.0). The median PFS was 7.0 months (95%CI: 5.0-8.9 months); median OS was 15.0 months (95%CI: 11.6-18.4 months). Of the 49 patients who completed the evaluation for tumor response, the ORR was 30.6% (95%CI: 17.2%-44.0%), and the disease control rate was 87.8% (95%CI: 78.2%-97.3%). The most common treatment-related adverse events (TRAEs) were leukopenia (98.0%), neutropenia (92%), and anemia (86.0%). Grade III/IV TRAEs included leukopenia (38.0%), neutropenia (32%), skin rash (6%), anemia (2.0%), mucositis (2%) and immune-related colitis (2%).Among them, the Grade III/IV immune-related adverse events irAEs) worthy of attention included were skin rash and immune-related colitis. There was no significant difference in PFS and OS among intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. Exploratory study showed that patients with CPS≥1 had longer PFS. However, there was no significant correlation between TMB and PFS. Conclusions: Toripalimab combined with gemcitabine and S-1 (GS) has shown good safety in the first-line treatment of advanced BTCs. Although the primary endpoint did not reach the preset goal, toripalimab plus GS as first-line treatment has shown encouraging data of PFS and OS in patients with advanced BTC, which is worthy for further verification. Biomarker analysis showed that the expression level of PD-L1 could predict the curative effect. Clinical trial information: NCT03796429.
Real-world treatment (tx) patterns and economic burden of patients (pts) with marginal zone lymphoma (MZL).
Authors: Keri Yang, Tom Liu, Boxiong Tang, Bijal D. Shah
Journal: Journal of Clinical Oncology (2022)

e18730 Background: MZL remains understudied with limited real-world evidence on how current tx conform to clinical guidelines. This study aimed to assess real-world tx patterns, costs, and healthcare resource utilization (HRU) in US MZL pts. Methods: A retrospective, observational study was conducted using the IBM MarketScan® commercial and Medicare supplemental claims dataset (2017-2020). Newly diagnosed adult MZL pts (≥18 yr) continuously enrolled 6 month pre- and 3 month post-index date, defined as the first diagnosis date, were included. Tx regimens were identified by line of therapy and mutually exclusively categorized as rituximab monotherapy (R-mono), bendamustine + rituximab (BR), rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib (ibr), or other. Descriptive analyses were conducted to assess pt sociodemographic/clinical characteristics and tx utilization patterns (frequency, duration, discontinuation). Costs and HRU assessed included inpatient, outpatient, and pharmacy visits per-patient-per-month (PPPM). Multivariable logistic regression was conducted to examine predictors of costs and HRU. Results: In 2491 MZL pts (median age = 63; 52% male), 59% were commercially insured (median age = 57) and 41% in Medicare (median age = 76). Common comorbidities were hypertension (44%), diabetes (17%), atrial fibrillation (AF; 16%), and gastroesophageal reflux disease (15%). Mean time from diagnosis to tx initiation was 223 days. A total of 1,781 (72%) pts received first-line (1L), 518 (29%) pts received second-line (2L) and 239 (13%) pts received third-line (3L) therapies. R-mono was the most common regimen across both commercial and Medicare pts and all tx lines (Table). R-CHOP and BR were the second most used regimen in 1L with decreased use in 2L+. Ibr was used more in 2L+ setting but had the lowest 1L PPPM cost (median $2958.9) than other regimens. Overall MZL pts had PPPM 4.6 outpatient visits, 0.5 hospitalization, and mean length of stay of 2.6 days. Total PPPM healthcare cost was $19,895.8. Multivariable regression showed that baseline comorbidities (AF, renal disease, neutropenia) and tx discontinuation were significant predictors of higher costs and HRU. Conclusions: This real-world data suggested that US MZL real-world tx pattern across lines of therapy follows the regimen recommendations by the National Comprehensive Cancer Network clinical practice guidelines and that MZL pts incur high economic burden. Future studies are needed to evaluate long-term outcomes and the impact of heterogenous MZL subtypes.[Table: see text]
A 107-gene Nanostring assay effectively characterizes complex multiomic gastric cancer molecular classification in a translational patient-derived organoid model.
Authors: Daniel Skubleny, Kieran Purich, Thomas Williams, Jim Wickware, Sunita Ghosh, Jennifer L. Spratlin, Dan E. Schiller, Gina Rayat
Journal: Journal of Clinical Oncology (2022)

4049 Background: Multi-omics profiling of gastric cancer (GC) has produced numerous molecular classification systems. However, widespread clinical implementation and testing of molecular subtypes are currently limited. Here, we develop, validate and implement a custom Nanostring assay capable of allocating GC molecular subtypes to clinical specimens in a translational patient-derived organoid model. Methods: Using publicly available whole-transcriptome data, machine learning models were developed to predict GC molecular subtypes from 376 Cancer Genome Atlas (TCGA) and 1797 Tumour Microenvironment Score (TME) patients. Models were generated using feature selection with 10-fold nested cross-validation. GC biopsies from 10 local patients were preserved in paraffin (tumour) and established as an organoid culture (organoid). Gene expression was measured using Nanostring. The allocation of molecular subtypes was internally and externally validated using gold-standard reference features in public databases comprising 2202 GC patients and 10 tumour-organoid pairs, respectively. We evaluated the concordance of tumour-organoid molecular subtypes and explored the correlation between subtype scores and in-vitro chemotherapy response. Results: Classification models for TCGA (57 genes) and TME (50 genes) predicted subtypes with an accuracy ± standard deviation of 89.46% ± 0.04 and 89.33% ± 0.02, respectively. Subtype assignment of microsatellite instability (MSI) in reference to capillary electrophoresis was found to have 99.3% [95% CI 97.4-99.9, n = 277] internal and 100% [95% CI 83.2-100, n = 20] external accuracy. In reference to Epstein-Barr Virus (EBV) in-situ hybridization, EBV type internal and external accuracy was 98.7% [95% CI 97.4-99.5, n = 552] and 100% [95% CI 83.2-100, n = 20], respectively. TCGA Genomically Stable (GS) scores followed a previously characterized enrichment of diffuse-type histology compared to intestinal-type in internal and external cohorts (Dunn’s Test, p &lt; 0.0001 and p &lt; 0.05, n = 1471 and n = 15, respectively). Statistically similar subtype scores (Paired Wilcoxon, p &gt; 0.05) were found for tumour-organoid pairs. Discordance occurred in three tumour-organoid pairs. In-vitro Drug Sensitivity Score was not statistically efficacious in any molecular subtype, but Pearson correlation identified increasing efficacy with increasing EBV and MSI scores. Conclusions: Patient-derived organoids generally recapitulate the molecular subtype of parent tumours; however, in specific cases, subtype discordance occurs. Although additional external validation is required, our 107 gene assay effectively captures multi-omics classification systems in GC and allows future inquiry into the prognostic and therapeutic implications of these molecular subtypes.
Productivity losses under various second-line recurrent or metastatic cervical cancer treatment scenarios in the United States.
Authors: Jie Ting, Turgay Ayer, Ozden Onur Dalgic, Melisa Erdogan, Emine Yaylali, Jagpreet Chhatwal
Journal: Journal of Clinical Oncology (2022)

e17520 Background: Recent data showed that a substantial proportion of second-line (2L)-eligible recurrent or metastatic cervical cancer (r/mCC) patients do not receive therapy. Additionally, although higher direct medical costs has been demonstrated with increasing r/mCC disease severity, there is no data on the impact of 2L treatment choices on societal costs. This study aims to estimate productivity loss due to untreated r/mCC and reduction in productivity losses associated with various 2L therapy options in the United States. Methods: We simulated the natural history of r/mCC by developing a Markov model with three stages: progression-free (PF), progressive (P), and death (D) for the course of r/mCC patients (average age: 50 years) during 2L treatment. We considered four treatment scenarios for patients who progressed on 1L systemic therapy: no 2L therapy, chemotherapy, overall 2L treatments (including option of cytotoxic monotherapy, immunotherapy, or other combination therapies), and tisotumab vedotin (TV). The model was parameterized and calibrated to match the overall survival and progression-free survival reported in recent clinical studies. Productivity loss associated with each disease stage was estimated by time spent at each stage, activity performance rate, and annual market and non-market productivity. Model outcomes included cumulative time spent in each stage and per patient 1-year and 5-year productivity losses. Results: Within a 1-year period, patients spend an estimated 6.1 months in the P stage under the no 2L treatment scenario; 4.4 months in PF and 4.3 months in P under 2L chemotherapy; 4.4 months in PF and 4.8 months P under overall 2L treatments scenario; and 5.7 months in PF and 4.3 months in P under TV scenario. Per person 1-year productivity under no 2L therapy was between $11.7K-$16.8K. As compared with no 2L therapy, 1-year per-person productivity improved by $5K-$14.6K under chemotherapy, by $5.8K-$15.6K under overall 2L treatments, and by $7.3-$19.9K under TV. When extending to a 5-year horizon, the projected cumulative per patient productivity improvement relative to that of patients with no 2L therapy ranged by $9.2K-$20.7K under chemotherapy, by $12.9K-$25.3K under overall 2L treatments, and by $19K-$36.9K under TV. Conclusions: Societal costs of 2L r/mCC in terms of lost productivity is substantially less in patients receiving 2L treatment vs. no treatment, within a 1-year period of becoming eligible for 2L therapy. Among patients receiving treatment (chemotherapy only or overall 2L treatment), we projected that society still incurs potentially meaningful lost productivity, relative to being treated with TV. TV’s 2021 approval in 2L r/mCC offers additional treatment option for patients, and continued efforts should be directed toward providing more treatment options in this setting.
Early intervention for high-risk and low-risk of progression for patients with smoldering multiple myeloma.
Authors: Nathan W. Sweeney, Christian S. Cheung, Thomas H. Molina, Jennifer M. Ahlstrom
Journal: Journal of Clinical Oncology (2022)

8058 Background: Previous studies have observed smoldering multiple myeloma (SMM) patients with a biomarker criteria of &gt; 20% bone marrow plasma cells, &gt; 2 g/dL M protein spike, and &gt; 20 free light chain ratio, also known as 20/2/20, are at a higher risk of progressing to multiple myeloma (MM) than others. These findings have ignited interest in pursuing early intervention for these high-risk patients. However, we asked if early intervention would be beneficial for all SMM patients regardless of the progression risk level. Methods: We utilized real-world data from HealthTree Cure Hub for Multiple Myeloma to first, determine whether 20/2/20 resulted in a higher risk of progression and second, analyze whether early intervention delayed progression from SMM to MM. A 2-sample t-test was used to compare 20/2/20 to non-20/2/20 patients, as well as in the comparison between SMM patients who received early intervention with treatment to without early intervention. Results: We found that patients who met at least two of the criteria of 20/2/20 had a tendency to progress to MM 35% faster than patients who did not meet the criteria (n = 36, p-value &lt; 0.10). While not significant, it’s still worth noting that there is a difference in the mean time to progression for these patients. Next, we found SMM patients who do not receive early intervention with treatment develop MM two times faster than those who do receive early intervention with treatment, regardless of progression risk level (n = 129, p-value &lt; 0.001). Conclusions: Our results revealed that at least two of the biomarker criteria could aid in the identification of patients with a higher risk of progression. However, a casual approach of “sit and wait” for patients to develop 20/2/20 is not warranted since our findings revealed that all SMM patients benefited from treatment intervention regardless of the progression risk level.
Non-hepatocellular carcinoma management: A SEER database analysis.
Authors: Ashton Legenza, Connor Tupper, Michael Burdyny, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e16108 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, however, chronic viral hepatitis and cirrhosis place patients at an increased risk for non-HCC malignancies as well. A major treatment option for these tumors is local tumor destruction via a number of minimally invasive techniques available to interventional radiologists. This study assessed the prognostic impact of various liver-directed local tumor therapies in the management of non-HCC liver cancer. Methods: We searched the SEER-18 database for malignant liver cancers not coded as HCC (8170-8175) that were diagnosed between 2000-2018. Patients were excluded if the cause of death was not associated with their cancer according to SEER’s cancer-specific death categorization. The SEER database tracks survival up to 60 months. SPSS was used for all descriptive and univariate survival statistics. Results: A total of 228 patients were collected from this search. 59.6% of cases were from males and the average age was 64 years old (median = 65). 60.1% were in non-Hispanic White patients, followed by Hispanic (16.2%), non-Hispanic Asian or Pacific Islander (14.0%), and non-Hispanic Black (9.2%) patients. Of the 170 patients with staging coded, 62.9% were local, 24.7% were regional, and 12.4% were distant. 36.8% of patients received some form of chemotherapy, while only 3.1% received radiation. When grouped by age range (&lt; 49, 50-69, 70+), survival did not differ between groups. Sex also did not influence survival (p = .325). Patients that received chemotherapy had worse outcomes, likely due to worse staging which was negatively associated with survival (p &lt; .05). Radiation did not significantly improve survival. Of the local tumor destruction therapies, Heat-Radio-Frequency ablation (RFA) (n = 150) improved survival significantly in comparison to: local tumor destruction not otherwise specified (n = 42), photodynamic therapy (n = 1), electrocautery (n = 4), cryosurgery (n = 4), and ultrasound or acetic acid (n = 15) (all p &lt; 0.05). Laser surgery (n = 3) and intratumoral injection of alcohol (n = 9) had no significant outcome differences. RFA had an estimated mean survival time of 35.7 months while all other interventional radiology modalities combined had a mean estimated survival time of 21.4 months (p &lt; .000). Conclusions: Though limitations of a small sample size and univariate statistical analyses were present in this study, RFA likely has improved survival compared to other interventional radiology modalities used in the treatment of non-HCC liver cancer.
Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy: A multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).
Authors: Lilian Schwarz, Jean-Baptiste Bachet, Aurelia Meurisse, Olivier Bouché, Eric Assenat, Guillaume Piessen, Eric Terrebonne, Pascal Hammel, Nicolas Regenet, Célia Turco, Julien Taieb, Jean-Yves Mabrut, Olivier Turrini, Fabienne Portales, Francois Paye, Louise Barbier, Stephanie Truant, Antonio Sa Cunha
Journal: Journal of Clinical Oncology (2022)

4134 Background: Despite the limited number of published RCTs, patients with resectable pancreatic adenocarcinoma (rPAC; NCCN criteria) seem to benefit from neoadjuvant (NAT) with regards to R0 resection rate, downstaging and survivals (PREOPANC-1; Preop-02/JSAP-05; NEONAX, SWOG05-15). Few prospective results are currently available concerning the completion of the full therapeutic sequence and oncological results. Methods: In the PANACHE01-PRODIGE48 prospective multicenter controlled non-comparative Phase II trial, 153 patients with rPDAC were randomized 2:2:1 to 4 cycles of NAT chemotherapy (mFOLFIRINOX; Arm1 or FOLFOX; Arm2) or upfront surgery (Ctrl_Arm) in 28 French centers from 02/2017 to 07/2020. Primary objective was to evaluate the safety and efficacy of two regimens of NAT chemotherapy. The main co-primary endpoints were 1y-OS rate after randomization and the rate of patients undergoing the full therapeutic sequence. Event-free survival (EFS) was used to evaluate the time to recurrence between groups. An event being defined as progression before surgery, unresectable or metastatic disease at surgical exploration, recurrence after surgery or death. Results: Of the 153 randomized patients, 146 were available for analysis (Arm1,n=70; Arm2,n=50; Ctrl_arm,n=26). In the Arm1 and 2, completion of the 4 planed cycles was 88.6 and 84%, respectively, with a dose reduction in 52% and 24%. The cumulative rates of grade 3/4/5 toxicity were 56.7 and 57.4%, respectively. The resection rates (RR) were 74, 68 and 81% respectively in Arm1, Arm2 and Ctrl_Arm. Respectively, 88.4, 91 and 85.7% of patients started adjuvant chemo. 1y-OS rates were respectively of 84.1, 71.8 and 80.8% in Arm1, Arm2 and Ctrl_Arm with a median follow-up in each group of 25.6, 33, 30.9 months. Following the intermediate analysis, the Arm2 was stopped for lack of efficacy (rejection of the H0 hypothesis for 1yOS). 1y-Event free survival (EFS) rates were 51.4% in Arm1, 43.1% in Arm2 and 41.7% in Ctrl_Arm, with corresponding median EFS of 12.4, 11 and 9.2 months. Conclusions: The feasibility and efficacy of the mFOLFIRINOX neoadjuvant chemotherapy is confirmed regarding completion of therapeutic sequence and oncological outcomes. These results confirm the rationale for ongoing clinical trials, PREOPANC3 and Alliance AO21806. Clinical trial information: NCT02959879.
Increased adherence to molecular profiling recommendations in non–small cell lung cancer through use of prior authorization and peer review.
Authors: Stephen A. Hamilton, Bhuvana Sagar, Kathryn Christensen, Anne Bowers, Tim Dollear
Journal: Journal of Clinical Oncology (2022)

9129 Background: National oncology guidelines advocate for broad molecular profiling to detect potentially actionable driver mutations prior to initiation of first-line therapy for patients with advanced non-small cell lung cancer (NSCLC). Results of genomic tests can confirm the presence of specific cancer tumor mutations that are best treated with more targeted therapies. Recent studies have shown that up to 30% of lung cancer patients may not receive the most effective treatment due to a lack of guideline-concordant genomic testing. We analyzed data from our prior authorization medical oncology program to determine adherence to national guidelines recommendations, and then developed a program to improve adherence to broad molecular profiling utilizing our proprietary prior authorization algorithms and our proactive peer consultation model. Methods: eviCore healthcare uses the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to support its proprietary program for medical oncology drug management, and requires attestation on the results of NCCN recommended genomic/molecular test results in advanced NSCLC during prior authorization of systemic therapy. In November 2019, we implemented a next-generation sequencing (NGS) testing results requirement for metastatic non-squamous NSCLC patients prior to first-line therapy approval. If testing had not been completed, a peer to peer consultation was performed to advocate for testing prior to initiation of chemoimmunotherapy regimens. The rate of appropriate tumor testing is defined by provider attestation of test results prior to initiation of therapy. We define the control period (pre- implementation) as October 2018 through September 2019 ( n = 667). The measurement period (post-implementation) is January 2020 through December 2020 ( n = 390). Results: From pre to post there was a 35% increase in testing adherence (p &lt; 0.001). After the testing requirement was implemented, the appropriate tumor testing rate increased to 99% by the second half of 2020, compared to the control period (62%). Additionally, after the testing requirement began, pembrolizumab utilization for advanced stage NSCLC decreased by a net 4.2% per month. This decrease in pembrolizumab utilization likely reflected patients being matched to more appropriate targeted therapy based on genomic testing results. Conclusions: We demonstrate that by combining medical oncology prior authorization with focused peer consultation, adherence to national society recommendations for broad molecular profiling prior to initiating first line therapy in advanced NSCLC can be significantly improved. By improving testing adherence, the most effective and appropriate therapy can be matched to the patient.